The association of mRNA with eukaryotic ribosomes is likely a multistep process involving complex interactions between the mRNA and proteins. Understanding the relationship of mRNA structure to initiation efficiency, cap dependence and AUG codon recognition is paramount in deciphering these important steps. Complete secondary structure models for eukaryotic mRNAs based on both structure data and thermodynamic criteria are scarce. We are determining complete secondary structure models for both mouse and rabbit Alpha and Beta globin mRNAs. Computer-aided predictions based on both thermodynamic energy minimizations and enzymatic and chemical structure data will likely generate reasonable models. The Alpha and Beta globin mRNAs represent a well documented translational system, whereby Beta globin mRNA initiates at a rate of 50% faster than Alpha mRNA within mammalian reticulocytes. The mouse and rabbit globin mRNAs can be purified in high enough quantities necessary to carry out these studies. We are also investigating secondary structure within the initiation regions for human and duck Alpha and Beta globin mRNA, as well as the plant viral mRNAs BMV 3 and 4, A1MV 3 and 4, and STNV RNA. The relative initiation efficiencies for these mRNA molecules have been investigated, and these structure studies will likely supplement our structure-function correlations. Since messenger RNA within mammalian cells normally exists in association with protein as a messenger ribonucleoprotein particles (mRNP), we are developing methods for isolation of pure and biologically intact rabbit and mouse globin mRNP. Determination of what proteins are associated with mRNA, as well as localizing their corresponding binding sites using photo-induced and chemical cross-linking, could likely identify important protein-mRNA interactions prior to ribosome binding. The secondary structure models will be invaluable, not only in defining the topographical and eventually functional organization of proteins on a mammalian mRNA, but also in detecting possible longrange tertiary interactions in the globin mRNAs.